This invention is generally in the field of capillary electrophoresis, and relates particularly to apparatus and method for substantially concurrently loading fluid samples to be analyzed into multiple capillary tubes of a multiplexed or xe2x80x9cparallelxe2x80x9d capillary electrophoresis system.
Capillary electrophoresis (CE) is a chemical separation technique involving the use of one or more capillary tubes. Parallel CE, a recently developed technique using many parallel capillary tubes, is growing in popularity since this technology allows multiple samples to be analyzed quickly and efficiently. This is particularly advantageous in combinatorial chemistry where many hundreds and even thousands of samples are analyzed over a short period of time. Parallel CE involves the use of a xe2x80x9cbundlexe2x80x9d of capillary tubes, e.g., 96 such tubes. A chemical sample to be analyzed is loaded in each tube, and a high voltage is applied to the tube, causing the components of the sample to migrate in the tube at different speeds, thereby causing separation of the components which can then be analyzed by conventional light absorption or other techniques. Reference may be made to the following patents and publications for a more detailed description of CE, including parallel CE, and various analytical techniques used in CE: U.S. Pat. Nos. 5,900,934, 5,324,401, 5,312,535, 5,303,021, 5,239,360; C. Culbertson et al., Analytical Chemistry, 70, 2629-2638 (1998); and X. Gong et al., Analytical Chemistry, 71(21); 4989-4996 (1999).
In prior multiplexed CE systems, the capillary tubes have been loaded with liquid samples either hydrostatically (i.e., by siphoning) or electrokinetically. However, these methods have various drawbacks, and there is a need for an improved loading system which is more reliable, reproducible and versatile.
Among the several objects of this invention may be noted the provision of a hydrodynamic injector for loading liquid samples into the inlet ends of multiple capillary tubes in preparation for a CE operation; the provision of such an injector which loads capillary tubes substantially concurrently and very quickly using a standard microtiter plate; the provision of such an injector which is easy to operate; the provision of such an injector which can be used to flush and condition the capillary tubes prior to sample loading; the provision of such an injector which is safe to use; the provision of two such injectors which can be used at opposite ends of the capillary tubes to enable loading from both ends of the tubes; and the provision of a method of simultaneously transferring liquid samples into the inlet ends of multiple capillary tubes to carry out a CE operation.
In general, the present invention is directed to a hydrodynamic injector for substantially concurrently loading fluid samples to be analyzed into multiple capillary tubes of a capillary electrophoresis system, the tubes having first and second ends. The injector comprises an enclosure defining a pressure chamber for holding multiple receptacles, each containing a fluid sample therein, and apertures in the enclosure for passing capillary tubes into a position wherein first ends of the tubes are positioned in the pressure chamber in fluid communication with the samples in respective receptacles. Electrodes on the enclosure extend into the pressure chamber for reception in the receptacles. The enclosure has a gas inlet for pressurizing the pressure chamber whereby the fluid samples are substantially concurrently forced from respective receptacles into the first ends of respective capillary tubes in preparation for a capillary electrophoresis operation.
The present invention is also directed to a hydrodynamic injector of the type described above where the enclosure comprises a channel surrounding the pressure chamber and communicating with the gas inlet, and passages connecting the channel and the pressure chamber at spaced intervals around the pressure chamber.
In another aspect, a hydrodynamic injector of the present invention comprises second enclosure having a second pressure chamber therein containing one or more receptacles for receiving fluid samples transmitted through the capillary tubes from the first enclosure, apertures in the second enclosure for passing said capillary tubes into a position wherein second ends of the tubes are positioned in the second pressure chamber for the flow of fluid into the one or more receptacles, and electrodes on the second enclosure extending into the second pressure chamber for reception in the one or more receptacles. The second pressure chamber is adapted for holding multiple receptacles, each containing a fluid sample therein. The second enclosure has a gas inlet for pressurizing the pressure chamber whereby the fluid samples in the second enclosure are simultaneously forced from respective receptacles into the second ends of respective capillary tubes in preparation for a capillary electrophoresis operation.
A method of this invention generally involves the substantially concurrent transfer of fluid samples from multiple receptacles into first ends of multiple capillary tubes. The method comprises positioning the first ends of the capillary tubes and the receptacles in a single pressure chamber so that the first ends are in fluid communication with the samples in the receptacles, pressurizing the pressure chamber to force fluid from the receptacles into the capillary tubes, and causing an electric current to flow through the capillary tubes and contents thereof to cause a first capillary electrophoresis operation.
In another embodiment, a method of the present invention further involves an additional step of positioning second ends of the capillary tubes in a second pressure chamber containing multiple receptacles for receiving the second ends.
In still another embodiment, the pressurizing step involves pressurizing an accumulator to a predetermined pressure and, after the predetermined pressure has been reached, opening a valve to establish gas flow communication between the accumulator and the pressure chamber to pressurize the pressure chamber.
Other objects and features of this invention will be in part apparent and in part pointed out hereinafter.